To complement these data, a second set of high-throughput methods are available to characterize the molecular and cellular states induced by pathway interactions under different experimental conditions. 2002), and genetic interactions ( Tong et al. First, recent technological developments have made it feasible to measure pathway structure systematically, using high-throughput screens for protein-protein ( Ito et al. However, pathway-specific models are now being supplemented with global data gathered for an entire cell or organism, by use of two complementary approaches. Typically, models are directed toward a cellular process or disease pathway of interest ( Gilman and Arkin 2002) and are built by formulating existing literature as a system of differential and/or stochastic equations. Such models promise to transform biological research by providing a framework to (1) systematically interrogate and experimentally verify knowledge of a pathway (2) manage the immense complexity of hundreds or potentially thousands of cellular components and interactions and (3) reveal emergent properties and unanticipated consequences of different pathway configurations. A variety of modeling environments have been developed to simulate biochemical reactions and gene transcription kinetics ( Endy and Brent 2001), cellular physiology ( Loew and Schaff 2001), and metabolic control ( Mendes 1997). Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.Ĭomputer-aided models of biological networks are a cornerstone of systems biology. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Cytoscape's software Core provides basic functionality to layout and query the network to visually integrate the network with expression profiles, phenotypes, and other molecular states and to link the network to databases of functional annotations. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework.
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